The use of interspecific hamster/mouse somatic cell hybrids has greatly extended our studies on the genetic basis of tumorigenesis. We have used hybrids to identify and chromosomally map specific genes involved in oncogenesis and to construct cell lines carrying isolated genetic elements of this complex multigene system for their further characterization. Recent studies have mapped receptor loci for the ecotropic and MCF viruses to different mouse chromosomes. Hybrids which lack specific receptor loci were used to describe the time course of virus inducibility from different endogenous proviral loci. Receptor loci for different leukemia viruses are also being identified and mapped in other species using cat/hamster and human/hamster hybrids. Finally, somatic cell hybrids are being analyzed by blot hybridization with molecularly cloned probes to describe the chromosomal localization of proviral and other cancer-related loci. These studies have resulted in the localization of MMTV proviral loci to 3 mouse chromosomes and xenotropic envelope-reactive sequences to almost all of the mouse chromosomes. Analysis of hybrids has provided specific map locations for various proto-oncogenes, for interferon structural genes, and for 4 loci representing preferred integration sites for retroviruses in tumors.